{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:05:33Z","timestamp":1753877133086,"version":"3.41.2"},"reference-count":40,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T00:00:00Z","timestamp":1572307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Greece and the ESCMID"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Voriconazole exhibits in vitro activity against Candida glabrata and Candida krusei (EUCAST\/CLSI epidemiological cut-off values 1\/0.25 and 1\/0.5\u2009mg\/L, respectively). Yet, EUCAST found insufficient evidence to set breakpoints for these species. We explored voriconazole pharmacodynamics (PD) in an in vitro dynamic model simulating human pharmacokinetics (PK).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Four C. glabrata and three C. krusei isolates (voriconazole EUCAST and CLSI MICs of 0.03\u20132\u2009mg\/L) were tested in the PK\/PD model simulating voriconazole exposures (t\u00bd \u223c6\u2009h q12h dosing for 3\u2009days). PK\/PD breakpoints were determined calculating the PTA for exposure indices fAUC0\u201324\/MIC associated with half-maximal activity (EI50) using Monte Carlo simulation analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fungal load increased from 3.60\u202f\u00b1\u202f0.35 to 8.41\u202f\u00b1\u202f0.24 log10 cfu\/mL in the drug-free control, with a maximum effect of \u223c1 log10 kill of C. glabrata and C. krusei isolates with MICs of 0.06 and 0.25\u2009mg\/L, respectively, at high drug exposures. The 72\u2009h log10 cfu\/mL change versus fAUC0\u201324\/MIC relationship followed a sigmoid curve for C. glabrata (R2=0.85\u20130.87) and C. krusei (R2=0.56\u20130.76) with EI50 of 49 (32\u201376) and 52 (33\u201378) fAUC\/MIC for EUCAST and 55 (31\u201396) and 80 (42\u2013152) fAUC\/MIC for CLSI, respectively. The PTAs for C. glabrata and C. krusei isolates with EUCAST\/CLSI MICs \u22640.125\/\u22640.06\u2009mg\/L were &gt;95%. Isolates with EUCAST\/CLSI MICs of 0.25\u20131\/0.125\u20130.5 would require trough levels 1\u20134\u2009mg\/L; isolates with higher MICs would not attain the corresponding PK\/PD targets without reaching toxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The in vitro PK\/PD breakpoints for C. glabrata and C. krusei for EUCAST (0.125\u2009mg\/L) and CLSI (0.06\u2009mg\/L) bisected the WT populations. Trough levels of &gt;4\u2009mg\/L, which are not clinically feasible, are necessary for efficacy against WT isolates.<\/jats:p><\/jats:sec>","DOI":"10.1093\/jac\/dkz425","type":"journal-article","created":{"date-parts":[[2019,9,24]],"date-time":"2019-09-24T12:18:06Z","timestamp":1569327486000},"source":"Crossref","is-referenced-by-count":3,"title":["Voriconazole efficacy against Candida glabrata and Candida krusei: preclinical data using a validated in vitro pharmacokinetic\/pharmacodynamic model"],"prefix":"10.1093","author":[{"given":"Maria-Ioanna","family":"Beredaki","sequence":"first","affiliation":[{"name":"Clinical Microbiology Laboratory, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Panagiota-Christina","family":"Georgiou","sequence":"additional","affiliation":[{"name":"Clinical Microbiology Laboratory, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Siopi","sequence":"additional","affiliation":[{"name":"Clinical Microbiology Laboratory, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lamprini","family":"Kanioura","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maiken Cavling","family":"Arendrup","sequence":"additional","affiliation":[{"name":"Unit of Mycology, Statens Serum Institut, Copenhagen, Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark"},{"name":"Department of Clinical Microbiology, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johan W","family":"Mouton","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Meletiadis","sequence":"additional","affiliation":[{"name":"Clinical Microbiology Laboratory, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece"},{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,10,29]]},"reference":[{"key":"2019103013322965500_dkz425-B1","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1097\/MCC.0b013e32833e84d2","article-title":"Epidemiology of invasive 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